This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In preliminary studies, we have shown that both HD negative and HD positive human embryonic stem cells are capable of differentiation to neuronal cells which express cytoskeletal structural proteins such as [unreadable]-III-tubulin and MAP2ab and glial cells which express the characteristic protein GFAP. Measurements of stem cell derived neurons indicate that their axons and dendrites are typically 1-2[unreadable]m in diameter, making them ideal targets for TXM imaging. We hypothesise that soft X-ray tomography imaging using the carbon K-edge in combination with immune-gold labelling of HTT fibrillar aggregates, organelles (such as mitochondria), and the cytoskeleton will be a powerful imaging approach for elucidating subtle structural changes within the neurons related to mutant HHT and may shed new light into the molecular the mechanisms that lead to neurodegeneration.